Forces Shaping the Fastest Evolving Regions in the Human Genome

Comparative genomics allow us to search the human genome for segments that were extensively changed in the last ~5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.

比较基因组学（Comparative Genomics）可用于在人类基因组中筛选自与黑猩猩的共同祖先分化后的约500万年间发生广泛改变，但在其他物种中高度保守的基因组片段，这类片段因此极可能具备生物学功能。本研究共鉴定出202个在脊椎动物中高度保守，但在人类中呈现出显著加速替换速率特征的基因组元件。这些元件大多位于非编码DNA区域，且常靠近与转录及DNA结合相关的基因。重测序（Resequencing）实验证实，5个加速程度最高的基因组元件在人类中发生了显著改变，而在其他灵长类动物中并无此类变化，人类中的替换次数是黑猩猩的7倍。这些加速演化的基因组元件，尤其是排名前五的元件，呈现出强烈的腺嘌呤（A）→鸟嘌呤（G）、胸腺嘧啶（T）→胞嘧啶（C）的核苷酸替换偏好，且不成比例地分布在端粒（Telomeres）附近的高重组率与高GC含量的基因组区域中，这提示其演化可能受到偏向性基因转换或等容区选择的影响。此外，在包含两个加速程度最高的区域的基因组区段中，也存在定向选择的相关证据。多种演化力量共同作用，推动了人类基因组中演化最快的那些基因组元件的加速演化。